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Biomedical subjects

V Hanf

Publications and source records attributed to V Hanf.

At least 19 recordsLinked to original sources
PubMed2003

Endometrial cancer.

Radical surgery including complete pelvic and para-arortic lymph node dissection (LND) is both the main therapeutic effort and the decisive staging procedure in patients with invasive endometrial cancer (EC) and should be performed in specialized institutions. Vaginal cuff brachytherapy holds little serious side effects and may be beneficial in preventing vaginal recurrences. External irradiation treatment no longer has a routine indication in primary therapy. The omission of retroperitoneal staging (LND) at primary surgery does not indicate adjuvant radiotherapy but rather second-effort surgery removing pelvic and para-aortic lymph-nodes. External radiotherapy should be reserved for fully staged patients with residual non-resectable tumor manifestation and/or nodal involvement in relation to the extent of tumor involvement and surgical intervention. Hormonal and cytotoxic therapy is experimental in the adjuvant setting. The first step in palliative systemic treatment should be the administration of endocrine therapy when the tumor expresses progesterone receptors and tumor manifestations are not acutely life-threatening. In other cases or when endocrine treatment fails chemotherapy may be considered, which is often limited due to its toxicity. Preferably, palliative hormonal and/or chemotherapy should be administered in controlled clinical trials.

Combined Modality Therapy↗
PubMed2002

[Are estrogens carcinogens?].

It is well accepted that unopposed estrogens increase the risk of developing endometrial cancer. A relationship between estrogen exposure and the risk for breast cancer is very probable. In addition, an association of long-term estrogen substitution and ovarian cancer risk has been postulated recently. Estrogens have been considered as typical tumor promotors. Due to their estrogen-receptor-mediated mitogenic activity, these steroids were supposed to increase the statistical probability of spontaneous mutations. Recent experimental findings, however, suggest that estrogen metabolites, in particular 4-hydroxyestrogens are capable of inducing DNA-damage and transforming mutations. The clinical relevance of these genotoxic properties of estrogens remains to be established, but could obtain great importance. First molecular-epidemiologic studies suggest that due to the specific activity of their estrogen metabolizing enzymes some women might produce relevant amounts of mutagenic estrogen metabolites, increasing their risk for breast-, endometrial- or ovarian cancer respectively. These findings might result in novel preventive strategies. The present data do not justify to abandon the practice of hormone replacement therapy with estrogens or estrogens plus progestins in non hysterectomised women. It seems to be wise, however, to restrict hormone replacement therapy to symptomatic women with a clear indication and, according to the actual trend, limit it temporarily.

Breast Neoplasms↗
PubMed2001

Substances with estrogenic activity in effluents of sewage treatment plants in southwestern Germany. 2. Biological analysis.

The proliferation test with human estrogen receptor-positive MCF-7 breast cancer cells (E-Screen assay) was applied for quantitative determination of total estrogenic activity in 24-h composite effluent samples from 16 municipal and two industrial sewage treatment plants (STPs) in the state of Baden-Württemberg, southwestern Germany. The estrogenic efficacy relative to the positive control, 17beta-estradiol, was between 26 and 74% (median, 48%) for the 16 municipal STPs. Estradiol equivalent concentrations (EEQs) were between 0.2 and 7.8 ng/L (median, 1.6 ng/L) and, thereby, were lower than those found in a pilot study, which revealed EEQs of greater than 10 ng/L in the effluents of two other STPs. The EEQs in 14 of the 16 effluent samples were very similar (0.9-3.3 ng/L), indicating a rather constant input of estrogenic substances via STPs into rivers. Additional activated charcoal filtration turned out to be very efficient in further eliminating estrogenic activity from effluents. The EEQs of the E-Screen assay and those calculated from the results of extensive chemical analysis using the estradiol equivalency factors determined for 13 natural and synthetic estrogenic substances were comparable for most of the effluent samples. 17beta-Estradiol, 17alpha-ethinylestradiol, and, to a lesser extent, estrone contributed to 90% or more of the EEQ value.

Charcoal↗
PubMed1999

Development of a sensitive E-screen assay for quantitative analysis of estrogenic activity in municipal sewage plant effluents.

A simplified proliferation test with human estrogen receptor-positive MCF-7 breast cancer cells (E-screen assay) was optimized and validated for the sensitive quantitative determination of total estrogenic activity in effluent samples from municipal sewage plants. After solid phase extraction of 1 l sewage on either 0.2 g polystyrene copolymer (ENV+) or 1 g RP-C18 material and removal of the solvent, analysis of the extracts in the E-screen assay could be performed without any clean-up step. This was even possible with untreated sewage. Parallel extraction of four sewage samples on both different solid phase materials gave comparable quantitative results in the E-screen. A blank sample did not induce cell proliferation. As additive behaviour of the estrogenic response of single compounds was proven for two different mixtures each containing three xenoestrogens, total estrogenic activity in the sewage samples, expressed as 17 beta-estradiol equivalent concentration (EEQ), could be calculated comparing the EC50 values of the samples with those of the positive control 17 beta-estradiol. The detection limit of the E-screen method was 0.05 pmol EEQ/l (0.014 ng EEQ/l), the limit of quantification 0.25-0.5 pmol EEQ/l (0.07-0.14 ng EEQ/l). In total, extracts of nine effluent and one influent sample from five different municipal sewage plants in South Germany were analyzed in the E-screen. All samples strongly induced cell proliferation in a dose-dependent manner which was completely inhibited by coincubation with 5 nM of the estrogen receptor-antagonist ICI 182,780. The proliferative effect relative to the positive control 17 beta-estradiol (RPE) was between 30 and 101%. 17 beta-Estradiol equivalent concentrations were between 2.5 and 25 ng/l indicating a significant input of estrogenic substances via sewage treatment plants into rivers.

Biological Assay↗
PubMed1999

Effects of single polychlorinated biphenyls on the morphology of cultured rat tubuli seminiferi.

The effects of single polychlorinated biphenyls (PCB) on isolated tubuli seminiferi of the rat were studied. Freshly isolated rat tubuli seminiferi were prepared according to their transillumination pattern, i.e. dark or pale. Tubuli seminiferi with the dark pattern included stages II to VIII and tubuli with the pale pattern represented stages IX to XIV and stage I of the seminiferous cycle. Afterwards, tubuli seminiferi were exposed to single polychlorinated biphenyls for 5 or 24 h in vitro. PCB 126, PCB 77, and PCB 118 were used in final parts per billion (p.p.b.) concentrations as determined by quantitative PCB analysis. Eventually, the specimens were plastic embedded, cut into semithin sections, stained, and morphology was evaluated by light microscopy. Single PCB congeners induced morphological alterations in cultivated rat tubuli seminiferi in a time- and stage-dependent manner. Effects comprised loosened intercellular contacts between germ cells and Sertoli cells as well as cellular fragmentation in the layer of round spermatids. Early spermiogenesis seems particularly susceptible to single PCB congeners in concentration of background magnitude. The target cell has still to be discovered.

Animals↗
PubMed1998

Tetraploidy and partial endoreduplication in a tripronuclear zygote obtained after intracytoplasmic sperm injection.

OBJECTIVE: To describe a peculiar combination of cytogenetic abnormalities in a tripronuclear zygote obtained after intracytoplasmic sperm injection (ICSI). DESIGN: Case report. SETTING: A university hospital. PATIENT(S): A couple with a 4-year history of primary infertility. Intracytoplasmic sperm injection was performed because of male factor infertility (oligoteratozoospermia). INTERVENTION(S): Ultrasound-guided transvaginal follicular aspiration. MAIN OUTCOME MEASURE(S): Chromosomal karyotype of a tripronuclear one-cell zygote. RESULT(S): Unexpectedly, a tetraploid [92,XXYY, end3, -18, end18] chromosome complement was found, indicating injection of a diploid spermatozoon carrying two Y chromosomes. The parental origin of the other abnormalities could not be determined. The missing chromosomes may be attributed either to a hypodiploid [44,YY,-18,-18] sperm cell or to a hypohaploid [22,X,-18] oocyte. The exact tetraploid count was restored by endoreduplication of two chromosomes. This event could have occurred in one and the same or in two different pronuclei. CONCLUSION(S): Cytogenetic analysis of multipronuclear zygotes appears useful for assessing the incidence of chromosomal abnormalities at the earliest stage of conception. In addition to other methods, it also may contribute to evaluation of the transmission of aberrations by spermatozoa from infertile men.

Adult↗
PubMed1997

Influence of nicotine on progesterone and estradiol production of cultured human granulosa cells.

The purpose of this study was to investigate the direct action of one of the main constituents of cigarette smoke on corpus luteum function. Progesterone and estradiol production were measured in the presence and absence of nicotine as free base or bitartrate salt with or without luteinizing hormone (LH) stimulation using radioimmunoassay in an in vitro granulosa cell culture system. Human granulosa cells were obtained from 19 patients undergoing in vitro fertilization embryo transfer treatment for infertility at the University Women's Hospital, Tübinge, Germany. Nicotine free base augmented estradiol secretion and inhibited progesterone secretion by human granulosa cells in a dose-dependent manner. Nicotine bitartrate had little effect on steroid secretion. If granulosa cells were stimulated with LH, both nicotine preparations suppressed estradiol secretion, however, only nicotine bitartrate additionally inhibited progesterone secretion. The results suggest that cigarette smoking specifically affects the control mechanisms of intraovarian processes which are responsible for normal luteal function.

Analysis of Variance↗
PubMed1996

Mercury in urine and ejaculate in husbands of barren couples.

Mercury concentrations in morning urine and ejaculate were detected in 80 husbands of women presenting for infertility treatment. Additionally, the number of their dental amalgam fillings was documented. A routine spermiogram was performed, from which a numerical "fertility index" was calculated. Urinary mercury concentrations were in the range of non-exposed populations, only minute Hg concentrations were determined in ejaculate, 75% of the semen sample concentrations were under the detection limit of 5 micrograms/l. In comparison, 7 proven fertile workers with occupational mercury exposure had elevated levels of mercury in their ejaculates (range 10-65 micrograms/l). No positive correlation could be established between subject mercury concentrations in urine or ejaculate and the quality of their semen, expressed as fertility index. Equally, no such correlation could be established between the fertility index and the number of their dental amalgam fillings. From these preliminary data no evidence can be derived for the alleged relation between the mercury burden from dental amalgam fillings and male fertility disorders.

Adult↗
PubMed1993

Serotonin induces progesterone release from human granulosa cells in a superfused granulosa cell system.

The dynamics of the release of progesterone (P) by human granulosa cells (GCs) was investigated in a granulosa cell-superfusion system using serotonin (5-HT), propranolol (PR), or mianserin (MI). Granulosa cells were obtained from 8 women undergoing in-vitro fertilization and embryo transfer. Progesterone was measured using radioimmunoassay. Serotonin (100 pMol) induced P release from human GCs. This effect was specifically blocked by 100 pMol MI whilst 100 pMol PR was ineffective in this condition. The results suggest, that the superfused GC system is suitable for studying the dynamics of steroid secretion by human GCs.

Adult↗
PubMed1993

Dioxins--a commentary on gynaecological aspects of recent research.

Dioxins are very toxic chemical compounds which are most likely carcinogenic and immunosuppressant in humans. Reproductive toxicity may occur at lower dose levels. Dioxins have been detected in mothers milk and fetal tissue. Experimental data suggest that placental function could be compromised by dioxins. Further research into the biological effects of this group of environmental contaminants is needed.

Abortion, Habitual↗
PubMed1993

Spontaneous and gonadotropin-releasing hormone induced human chorionic gonadotropin release from superfused JAR choriocarcinoma cells.

JAR choriocarcinoma cells have retained several characteristics of normal trophoblasts and have been used as an in vitro trophoblast model. The superfusion system is suitable for the study of hormone synthesis and/or secretion. JAR cells were cultured and transferred to the superfusion system in order to evaluate the spontaneous hCG secretion and the effect of GnRH. The spontaneous hCG release showed a periodic pattern with a 48 min phase interval. In our system single cells and cell-clusters were superfused and there is a possibility that cell to cell connections might have an influence on the regulation of hormone synthesis and/or secretion. GnRH in 4 x 10(-7) M and 4 x 10(-6) M concentrations or 100 mM KCl caused an immediate hCG release from the JAR cells Repeated administration of GnRH resulted in a delayed hCG release which is probably related to the relatively small amount of hCG available from the storage granules or to the phase of spontaneous secretion.

Cell Line↗
PubMed1993

Relationship between the monoamine and gonadotropin content in follicular fluid of preovulatory graafian follicles after superovulation treatment.

Noradrenaline (NA), serotonin (5HT), dopamine (DA), FSH, LH and prolactin (PRL) content was determined in 104 preovulatory follicular fluids obtained from 44 patients undergoing in vitro fertilization. The patients were given human menopausal gonadotropin (HMG) for ovarium stimulation, ovulation was induced with 10000 IU human chorionic gonadotropin (HCG) 34-36 hours prior to the follicular aspiration by vaginal ultrasound. Classification of the oocytes was performed by direct microscopic evaluation differentiating three groups of oocytes: Group I.: prophase I; Group II.: metaphase I; Group III.: metaphase II. There was no significant difference in monoamine and FSH content of follicular fluid at different stage of the oocyte maturation. LH and PRL significantly increased parallel with oocyte maturation (38.9; 48.8; 56.7 IU/l and 1324; 2382; 3134 IU/l). significant negative correlation was observed in Group I. between 5HT-LH (r = -0.64); in Group II. between NA-LH (r = -0.62) and NA-PRL (r = -0.51). Significant positive correlation were found in Group I. between FSH-LH (r = 0.63), in Group II. between LH-PRL (r = 0.56), in Group III. between NA-5HT (r = 0.66), NA-DA (r = 0.80) and 5HT-DA (r = 0.66). These observations suggest that action of LH and PRL may be negatively modulated by 5HT and NA in the final stage of oocyte maturation.

Adult↗
PubMed1993

Relationship between the monoamine, progesterone and estradiol content in follicular fluid of preovulatory graafian follicles after superovulation treatment.

We measured the progesterone, estradiol (E2), serotonin (5-HT), noradrenaline (NA) and dopamine (DA) contents of follicular fluid (FF) samples obtained from 35 patients undergoing in vitro fertilization and embryo transfer. Progesterone and E2 were determined by radioimmunoassay, and monoamines were measured by a spectrofluorimetric method. Significantly higher progesterone and NA levels were found (p < 0.01) in FF from cycles in which the oocyte cleaved and resulted in pregnancy compared to FF containing uncleaved oocytes. NA and DA contents were significantly higher in FF from cycles resulting in pregnancy than in FF containing cleaved oocytes not resulting in pregnancy (p < 0.01). There were significantly lower NA and 5-HT levels in FF containing uncleaved oocytes compared to the latter group (p < 0.05). Significant positive correlations were found between progesterone and 5-HT (r = 0.67) and between NA and DA (r = 0.93) in the pregnant group; between progesterone and E2 (r = 0.84) in FF containing uncleaved oocytes; between progesterone and E2 (r = 0.71) and between NA and DA (r = 0.62) in FF from cycles in which the oocyte cleaved but did not result in pregnancy. The results suggest that the follicular hormonal changes associated with oocyte maturation may be locally modulated by monoamines.

Biogenic Monoamines↗
PubMed1993

Effect of noradrenaline and dopamine on progesterone and estradiol secretion of human granulosa cells.

The aim of this study was to explore the direct action of noradrenaline and dopamine on progesterone and estradiol secretion of human granulosa cells cultured in serum-free medium. Progesterone and estradiol production was measured in the presence and absence of noradrenaline, dopamine or propranolol using radioimmunoassays; statistical analysis was performed by analysis of variance and Newman-Keul's multiple range test. Twenty-six women aged 31 +/- 3 years undergoing in vitro fertilization and embryo transfer for infertility treatment at University Women's Hospital, University of Tübingen, Germany, took part in this study. Noradrenaline significantly inhibited progesterone production by human granulosa cells in a dose-related manner at a concentration of 10(-4)-10(-6) mol/l. Dopamine significantly stimulated estradiol secretion by granulosa cells in an inverse dose-related manner. Both effects were blocked by propranolol. The results suggest that catecholaminergic actions switch over the steroid production of human granulosa cells cultured in serum-free medium from progesterone to estradiol.

Adult↗